Brucker Sara Yvonne, Frank Liliane, Eisenbeis Simone, Henes Melanie, Wallwiener Diethelm, Riess Olaf, van Eijck Barbara, Schöller Dorit, Bonin Michael, Rall Kristin Katharina
Department of Women's Health, Center for Rare Female Genital Malformations, Women's University Hospital, Tübingen University Hospital, Tübingen, Germany.
Department of Women's Health, Research Center for Women's Health, University Tübingen, Tübingen, Germany.
Acta Obstet Gynecol Scand. 2017 Nov;96(11):1338-1346. doi: 10.1111/aogs.13202. Epub 2017 Sep 21.
Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) is characterized by congenital absence of the uterus and the upper two-thirds of the vagina in otherwise phenotypically normal females. It is found isolated or associated with renal, skeletal and other malformations. Despite ongoing research, the etiology is mainly unknown. For a long time, the hypothesis of deficient hormone receptors as the cause for MRKHS has existed, supported by previous findings of our group. The aim of the present study was to identify unknown genetic causes for MRKHS and to compare them with data banks including a review of the literature.
DNA sequence analysis of the oxytocin receptor (OXTR) and estrogen receptor-1 gene (ESR1) was performed in a group of 93 clinically well-defined patients with uterovaginal aplasia (68 with the isolated form and 25 with associated malformations).
In total, we detected three OXTR variants in 18 MRKHS patients with one leading to a missense mutation, and six ESR1 variants in 21 MRKHS patients, two of these causing amino acid changes and therefore potentially disease.
The identified variants on DNA level might impair receptor function through different molecular mechanisms. Mutations of ESR1 and OXTR are associated with MRKHS. Thus, we consider these genes potential candidates associated with the manifestation of MRKHS.
迈耶-罗基坦斯基-库斯特-豪泽综合征（MRKHS）的特征是在其他方面表型正常的女性中先天性子宫和阴道上三分之二缺失。它可单独出现或与肾脏、骨骼及其他畸形相关。尽管研究不断，但病因主要仍不明。长期以来，我们团队之前的研究结果支持了激素受体缺陷作为MRKHS病因的假说。本研究的目的是确定MRKHS未知的遗传病因，并将其与数据库进行比较，包括文献综述。
对一组93例临床明确诊断为子宫阴道发育不全的患者（68例为孤立型，25例伴有相关畸形）进行了催产素受体（OXTR）和雌激素受体-1基因（ESR1）的DNA序列分析。
我们总共在18例MRKHS患者中检测到3种OXTR变异，其中1种导致错义突变；在21例MRKHS患者中检测到6种ESR1变异，其中2种导致氨基酸改变，因此可能致病。
在DNA水平上鉴定出的变异可能通过不同的分子机制损害受体功能。ESR1和OXTR的突变与MRKHS相关。因此，我们认为这些基因是与MRKHS表现相关的潜在候选基因。
